Calmangafodipir Reduces Sensory Alterations and Prevents Intraepidermal Nerve Fibers Loss in a Mouse Model of Oxaliplatin Induced Peripheral Neurotoxicity
| Autor: | Laura Monza, Jacques Näsström, Eleonora Pozzi, Paola Marmiroli, Guido Cavaletti, Norberto Oggioni, G Fumagalli, Annalisa Canta, Alessia Chiorazzi, Virginia Rodriguez-Menendez, Cristina Meregalli, Valentina Alda Carozzi |
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| Přispěvatelé: | Canta, A, Chiorazzi, A, Pozzi, E, Fumagalli, G, Monza, L, Meregalli, C, Carozzi, V, Rodriguez Menendez, V, Oggioni, N, Nasstrom, J, Marmiroli, P, Cavaletti, G |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
IENF density
Physiology Clinical Biochemistry cold hyperalgesia Sensory system Nerve fiber Pharmacology medicine.disease_cause Biochemistry Article 03 medical and health sciences 0302 clinical medicine neurotoxicity medicine Mangafodipir calmangafodipir Molecular Biology Chemistry lcsh:RM1-950 oxaliplatin Neurotoxicity Cell Biology medicine.disease Oxaliplatin Peripheral lcsh:Therapeutics. Pharmacology Calmangafodipir medicine.anatomical_structure 030220 oncology & carcinogenesis 030217 neurology & neurosurgery Oxidative stress medicine.drug mechanical allodynia |
| Zdroj: | Antioxidants Volume 9 Issue 7 Antioxidants, Vol 9, Iss 594, p 594 (2020) |
| ISSN: | 2076-3921 |
| DOI: | 10.3390/antiox9070594 |
| Popis: | Oxaliplatin (OHP) is an antineoplastic compound able to induce peripheral neurotoxicity. Oxidative stress has been suggested to be a key factor in the development of OHP-related peripheral neurotoxicity. Mangafodipir, a contrast agent possessing mitochondrial superoxide dismutase (MnSOD)-mimetic activity, has been tested as a cytoprotector in chemotherapy-induced peripheral neurotoxicity (CIPN). Calmangafodipir (PledOx® ) has even better therapeutic activity. We investigated a BALB/c mouse model of OHP-related CIPN and the effects of the pre-treatment of calmangafodipir (2.5, 5, or 10 mg/kg intravenously) on sensory perception, and we performed a pathological study on skin biopsies to assess intraepidermal nerve fiber (IENF) density. At the end of the treatments, OHP alone or in pre-treatment with calmangafodipir 2.5 and 10 mg/kg, induced mechanical allodynia and cold thermal hyperalgesia, but calmangafodipir 5 mg/kg prevented these effects. Accordingly, OHP alone or in pre-treatment with calmangafodipir 2.5 and 10 mg/kg, induced a significant reduction in IENF density, but calmangafodipir 5 mg/kg prevented this reduction. These results confirm a protective effect of calmangafodipir against OHP-induced small fiber neuropathy. Interestingly, these results are in agreement with previous observations suggesting a U-shaped effect of calmangafodipir, with the 10 mg/kg dose less effective than the lower doses. |
| Databáze: | OpenAIRE |
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